1. Phosphoproteomics Reveals the Wolframin-Calcium Axis as an Important Pathogenic Signaling Node in Primary Aldosteronism
- Author
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Linqiang Ma, Shumin Yang, Yi Yang, Xiangjun Chen, Jun Yang, Yifan He, Qingfeng Cheng, Junlong Li, Bing Kang, Siying Tang, Aipin Zhang, Xiaoyu Shu, Xiaoyu Li, Hang Shen, Ying Jing, Ying Song, Qifu Li, and Jinbo Hu
- Subjects
Internal Medicine - Abstract
Background: Aldosterone-producing adenoma (APA) is a benign adrenal tumor with autonomous aldosterone production which causes hypertension and excess cardiovascular risk. Protein phosphorylation regulates aldosterone secretion from adrenal cortical cells, but how signaling networks are remodeled in APA remains unknown. Methods: We performed an integrated proteomic and phosphoproteomic profiling of 15 APA and 10 matched nonfunctioning adrenocortical tumors (NFAT) based on the 4-dimensional label-free technique. We further validated our main findings in enlarged APA samples, mice, and adrenocortical cell line. Results: The proteomic and phosphoproteomic profiling of APA and NFAT quantified 5989 proteins and 9011 phosphopeptides. We highlighted differentially expressed and phosphorylated proteins which modulated aldosterone synthesis and secretion from APA. As intracellular calcium is the central signal for aldosterone synthesis, our integrated calcium signaling network implicated wolframin in the control of calcium influx and CYP11B2 (aldosterone synthase) activation in APA (ratio of wolframin expression in APA to NFAT: 6.411, P Conclusions: Wolframin is a regulatory protein in aldosterone hypersecretion. Remodeled calcium transportation and mitochondrial function are involved in wolframin-related aldosterone secretion.
- Published
- 2023